1. Academic Validation
  2. Correcting CFTR folding defects by small-molecule correctors to cure cystic fibrosis

Correcting CFTR folding defects by small-molecule correctors to cure cystic fibrosis

  • Curr Opin Pharmacol. 2017 Jun;34:83-90. doi: 10.1016/j.coph.2017.09.014.
Marjolein Mijnders 1 Bertrand Kleizen 1 Ineke Braakman 2
Affiliations

Affiliations

  • 1 Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Science for Life, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, The Netherlands.
  • 2 Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Science for Life, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, The Netherlands. Electronic address: i.braakman@uu.nl.
Abstract

Pharmacological intervention to treat the lethal genetic disease cystic fibrosis has become reality, even for the severe, most common folding mutant F508del CFTR. CFTR defects range from absence of the protein, misfolding that leads to degradation rather than cell-surface localization (such as F508del), to functional chloride-channel defects on the cell surface. Corrector and potentiator drugs improve cell-surface location and channel activity, respectively, and combination therapy of two correctors and a potentiator have shown synergy. Several combinations are in the drug-development pipeline and although the primary defect is not repaired, rescue levels are reaching those resembling a cure for CF. Combination therapy with correctors may also improve functional CFTR mutants and benefit patients on potentiator therapy.

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